A Rare Case of Plantar Epithelioma Cuniculatum Arising from a Wart.

A 68-year-old man, a known case of hypertension, coronary artery disease and old cardiovascular accident with right-sided hemiplegia, came with the chief complaints of a large cauliflower like growth with pus discharge on the left heel since 15 years. The patient had sustained a penetrating injury by a thorn on the left heel region few days before the lesion appeared. Dermatological examination revealed a single verrucous lesion measuring 7 × 7 cm on the left heel region associated with discharge of foul smelling cheesy material. There was also a enlarged right inguinal lymph node which was non-tender, firm, measuring 2 cm in diameter with normal overlying skin. X-ray left ankle was done which showed some soft tissue swelling. A skin biopsy showed hyperkeratosis, acanthosis and parakeratosis. Elongated rete ridges with keratinocyte hyperplasia, forming a large mass pressing on the underlying dermis were seen. There was formation of multiple large keratin filled invaginations and crypts. No atypical cells were seen. Based on history, clinical examination and investigations, a diagnosis of epithelium cuniculatum type of verrucous squamous cell carcinoma was made. A wide excision with a flap cover was performed in consultation with the oncosurgeon and the excision sample was sent for histopathological re-examination, which confirmed the diagnosis of epithelioma cuniculatum.

What was known?

Plantar epithelioma cuniculatum is a rare occurrence

Aetiology is only speculative.

Introduction

Verrucous carcinoma was a term originally used by Ackerman over 60 years ago to describe an indolent and abnormal variant of squamous cell carcinoma. Depending on the anatomical site, there are presently three main forms of verrucous carcinoma which are described: Oral florid papilloma, giant condyloma acuminatum, and epithelioma cuniculatum.[12] Epithelioma cuniculatum is a rare variant of verrucous carcinoma which was first described by Aird et al., in 1954.[3] There are only a few cases of epithelioma cuniculatum reported worldwide and lesser so in India. We hereby report one such rare case of epithelioma cuniculatum arising from a wart.

Case Report

A 68-year-old man, a known case of hypertension, coronary artery disease and old cardiovascular accident with right sided hemiplegia, came with the chief complaints of a large cauliflower-like growth with pus discharge on the left heel since 15 years. The patient was apparently alright 15 years back when he sustained a penetrating injury by a thorn on the left heel region. A few days later he developed a small elevated lesion at the site which was associated with some pain. He consulted a local doctor who prescribed him some medicines and later superficially excised it. He thereafter had three to four episodes of increase in the size of lesion, each episode being treated with paring. Presently he had gradual increase in the size of the lesion since the last 6 months. It was associated with discharge of foul-smelling secretion. There was no history of prolonged fever, weight loss, chronic cough, family or personal history of Koch's.

On dermatological examination, there was a single verrucous lesion measuring 7 × 7 cm on the left heel region associated with discharge of foul-smelling cheesy material [Figure 1]. There was also an enlarged right inguinal lymph node which was non-tender, firm, measuring 2 cm in diameter with normal overlying skin. Systemic and general examination was within normal limits. The differential diagnoses that were considered at this stage were epithelioma cuniculatum, tuberculosis verrucosa cutis, chromoblastomycosis and large plantar verruca.

Figure 1

Clinical images: (a) Large exophytic growth on left heel. (b) Close up revealing the friable portions with deep fissures

Routine hematological, biochemical and serological investigations were within normal limits. X-ray left ankle was done which showed some soft tissue swelling. X-ray chest PA view was within normal limits. Mantoux test was negative. Pus culture from the lesion showed a growth of Pseudomonas aeruginosa which was found sensitive to levofloxacin. Fungal and mycobacterial culture were negative. ELISA for HIV and serum VDRL was negative. FNAC from the lymph node was reactive.

A skin biopsy showed massive hyperkeratosis, papillomatosis and parakeratosis. Elongated rete ridges with keratinocyte hyperplasia, forming a large mass, pressing on the underlying dermis, were seen. There was formation of multiple large keratin-filled cysts and crypts with rabbit-burrow like invaginations along with an inflammatory infiltrate consisting of lymphocytes and neutrophils [Figure 2]. The tumor was sharply demarcated by an intact basement membrane and the keratinocytes appeared well differentiated without any signs of nuclear atypia or loss of polarity. Certain sections of the tumor showed the characteristic features of warts, namely koilocytes [Figure 3]. PAS stain revealed no fungal elements. A wide excision with flap cover was performed in consultation with the oncosurgeon and the excision sample was sent for histopathological re-examination, which confirmed the diagnosis of epithelioma cuniculatum. The patient is on regular follow up and has not shown any recurrence 3 months post surgery.

Figure 2

Histopathology revealing: (a) Massive hyperkeratosis, papillomatosis, acanthosis and parakeratosis along with characteristic crypts, keratin cysts and intact basement membrane [H and E, ×10]. (b) High power view showing the keratin cysts, crypts and the inflammatory infiltrate [H and E, ×40]

Figure 3

(a and b) Portions of the section showing koilocytes [H and E, ×40]

Discussion

The word epithelioma means “tumor of the epithelium” and cuniculate refers to crypt-like spaces seen on histology that resemble rabbit burrows. Epithelioma cuniculatum is a rare variant of verrucous carcinoma localized to the plantar surface and is a low-grade malignancy. Various etiological factors like trauma, chronic irritation, thorn prick and HPV infection have been implicated. Others have described the occurrence of this tumor in chronic ulcers in leprosy and diabetes mellitus.[45] The HPV types associated with verrucous carcinoma include low-risk HPV types 6 and 11 and high-risk types HPV 16 and 18, which can be identified by PCR or DNA dot blot hybridization. HPV types 2 and 16 have been identified as etiological factors in two cases.[67] Our patient could not afford these investigations and was therefore not done.

Most patients present in their 5–6th decades, with a predominance for men. When feet are affected, the tumor usually occurs predominantly on the anterior weight-bearing part of the sole of the foot, which was not so in our case. There is usually a delay in diagnosis due to the resemblance of the lesion to a wart or corn, which grows progressively despite topical treatment. The median time to diagnosis was 13 years, in one study and 16 years in another case series.[8] Although it has a negligible incidence of metastasis, it is known for its aggressive local invasion, compressing underlying soft tissue but lacking destructiveness. Patients with verrucous carcinoma usually have a favorable prognosis with 5-year survival rates of 75%.[9] Distant metastasis is rare and mortality is therefore also very rare.[10] Treatment is by wide local excision with at least a 5-mm tumor-free margin.

Differential diagnosis include verruca vulgaris, reactive epidermal hyperplasia, adnexal tumors, giant seborrheic keratosis, giant keratoacanthoma, eccrine poroma, hyperkeratotic basal cell epithelioma, verruciform xanthoma and cutaneous squamous cell carcinoma. Classical epithelioma cuniculatum is a well-demarcated exophytic white growth with fine papillary structure on the cut section. Under a microscope, there is both exophytic and endophytic proliferation of well-differentiated squamous epithelium. There is also pronounced hyper and parakeratosis in the downward extensions, which may be bullous rather than sharply pointed. It runs a protracted course. Viral warts do not show endophytic zones and usually have keratohylin granules. They do not grow over many years and have a tendency toward spontaneous regression. Keratoacanthoma is usually not verrucous in appearance and has a rapid self-limiting course. Microscopically it shows a large keratin-filled crater with upward and downward proliferation of epithelium from the crater. Individual cell keratinization and horn pearls may also be seen. Pseudocarcinomatous hyperplasia is a reactive process to a causative factor and rarely causes difficulty in differentiating from verrucous carcinoma. Differentiating these conditions becomes even more difficult if only superficial biopsies are taken. Multiple biopsies and a close clinical correlation are therefore required before a definite diagnosis is possible.

This case is interesting on the following counts: Occurrence on the heel, features of warts present even when the lesion has become very large and hyperkeratotic, and also because the condition is itself very rarely reported from this part of the world.

What is new?

Plantar epithelioma cuniculatum may not be as rare as reported in Indian literature

Plantar warts may be the precursors of epithelioma cuniculatum

Histopathological proof of koilocytes can establish human papilloma virus as the etiology.